X-100824251-G-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001325.3(CSTF2):c.696G>C(p.Gln232His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,203,898 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000016 ( 0 hom. 7 hem. )

Consequence

CSTF2
NM_001325.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

CSTF2 (HGNC:2484): (cleavage stimulation factor subunit 2) This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs. [provided by RefSeq, Jul 2008]

CSTF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17329317).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSTF2	NM_001325.3 link	c.696G>C	p.Gln232His	missense_variant	Exon 6 of 14	ENST00000372972.7	NP_001316.1	P33240-1
CSTF2	NM_001306206.2 link	c.696G>C	p.Gln232His	missense_variant	Exon 6 of 15		NP_001293135.1	E7EWR4B3V096B4DUD5
CSTF2	NM_001306209.2 link	c.696G>C	p.Gln232His	missense_variant	Exon 6 of 14		NP_001293138.1	P33240-2B4DUD5
CSTF2	XM_047441854.1 link	c.696G>C	p.Gln232His	missense_variant	Exon 6 of 10		XP_047297810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSTF2	ENST00000372972.7 link	c.696G>C	p.Gln232His	missense_variant	Exon 6 of 14	1	NM_001325.3	ENSP00000362063.2	P33240-1
CSTF2	ENST00000415585.7 link	c.696G>C	p.Gln232His	missense_variant	Exon 6 of 15	1		ENSP00000387996.2	E7EWR4
CSTF2	ENST00000413437.1 link	c.669G>C	p.Gln223His	missense_variant	Exon 6 of 6	5		ENSP00000415705.1	A0A0A0MT56
CSTF2	ENST00000475126.5 link	n.696G>C		non_coding_transcript_exon_variant	Exon 6 of 14	5		ENSP00000432060.1	E9PID8

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112307

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34463

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000940

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000859

AC:

AN:

174632

Hom.:

AF XY:

0.000100

AC XY:

AN XY:

59836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1091591

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

357505

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000529

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112307

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34463

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000940

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.696G>C (p.Q232H) alteration is located in exon 6 (coding exon 6) of the CSTF2 gene. This alteration results from a G to C substitution at nucleotide position 696, causing the glutamine (Q) at amino acid position 232 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.098

.;T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;M;.

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.69

MutPred

0.20

Gain of catalytic residue at L234 (P = 0.0742);Gain of catalytic residue at L234 (P = 0.0742);.;

MVP

0.53

MPC

1.4

ClinPred

0.29

GERP RS

3.6

Varity_R

0.77

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over